User login
The majority of postapproval clinical trials conducted by pharmaceutical companies explored novel or expanded uses as opposed to monitoring original indications, according to results from a cross-sectional study.
“The U.S. Food and Drug Administration can use postmarketing requirements to mandate pharmaceutical companies to conduct clinical trials after the approval of novel therapeutics,” wrote Joshua J. Skydel of Tufts University, Boston, and colleagues in JAMA Network Open.
“From 2009 through 2012, the FDA approved 110 novel therapeutics for 120 indications,” the researchers reported.
Of those approved, 37 novel agents were identified that lacked requirements for postmarket monitoring. Data was obtained from the Drugs@FDA database and consisted of industry-sponsored postapproval clinical studies conducted in the United States.
Postapproval study information included 600 trials registered on ClinicalTrials.gov that were primarily aimed at producing additional efficacy and safety data in approved or unapproved uses. The majority of these trials were for novel therapeutics being evaluated in oncology- and hematology-related indications.
After analysis, the researchers found that most of these trials examined agents for novel or expanded indications (60.5%) or widened populations of the initially indicated condition (20.3%).
In addition, several of these studies were nonrandomized (59.8%), had small sample sizes (median, 44 participants), and did not include comparators (63.5%).
“Among 600 trials, only 12.0% exclusively evaluated the originally approved indication,” the authors wrote.
The researchers acknowledged that a key limitation of the study was the inclusion of only postapproval clinical studies affiliated with pharmaceutical companies.
“The FDA may need to impose additional postmarketing requirements to generate further evidence for the original indications,” they concluded.
The study was funded by the Tufts University School of Medicine and the Laura and John Arnold Foundation. The authors reported financial affiliations with Johnson & Johnson, Medtronic, the Blue Cross Blue Shield Association, the National Institutes of Health, the Laura and John Arnold Foundation, and the Food and Drug Administration.
SOURCE: Skydel JJ et al. JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410.
One question that remains from the study by Skydel et al. is why the Food and Drug Administration did not mandate postapproval clinical studies for more than one-third of the novel agents approved from 2009 to 2012.
Among 600 postapproval trials affiliated with pharmaceutical companies, the vast majority were for novel therapeutics being studied in oncology- and hematology-related indications. Many of these premarket trials are one-arm, nonrandomized studies approved with evidence from surrogate outcomes. Recent studies have revealed that many novel agents do not show an overall survival benefit 5 years post approval.
From a clinical perspective, interpreting safety and efficacy data from these trials is challenging because of various limitations, including small sample sizes, no control groups, and lack of randomization. High-quality evidence helping clinicians determine which patients will benefit from these novel therapeutics is needed.
In addition, the purpose of these sponsored studies has come into question. While they can be used to generate further clinical data, many other reasons are possible. The expectation could be that once these studies are complete, clinicians may prescribe the agent being examined, thereby increasing off-label prescribing. Recent studies have revealed that off-label prescribing has the potential to increase the risk of drug-related adverse events.
“Postapproval studies need to advance clinical care by answering unresolved questions,” Dr. Lexchin wrote. “Clinicians and patients deserve better.”
Joel Lexchin, MD, is associated with the School of Health Policy and Management at York University in Toronto. He reported financial affiliations with the Gordon and Betty Moore Foundation, the Government of Canada, the Ontario Supporting Patient Oriented Research Support Unit, the St Michael’s Hospital Foundation, the Canadian Institutes of Health Research, and the American Diabetes Association. These comments are adapted from his editorial. (JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410 ).
One question that remains from the study by Skydel et al. is why the Food and Drug Administration did not mandate postapproval clinical studies for more than one-third of the novel agents approved from 2009 to 2012.
Among 600 postapproval trials affiliated with pharmaceutical companies, the vast majority were for novel therapeutics being studied in oncology- and hematology-related indications. Many of these premarket trials are one-arm, nonrandomized studies approved with evidence from surrogate outcomes. Recent studies have revealed that many novel agents do not show an overall survival benefit 5 years post approval.
From a clinical perspective, interpreting safety and efficacy data from these trials is challenging because of various limitations, including small sample sizes, no control groups, and lack of randomization. High-quality evidence helping clinicians determine which patients will benefit from these novel therapeutics is needed.
In addition, the purpose of these sponsored studies has come into question. While they can be used to generate further clinical data, many other reasons are possible. The expectation could be that once these studies are complete, clinicians may prescribe the agent being examined, thereby increasing off-label prescribing. Recent studies have revealed that off-label prescribing has the potential to increase the risk of drug-related adverse events.
“Postapproval studies need to advance clinical care by answering unresolved questions,” Dr. Lexchin wrote. “Clinicians and patients deserve better.”
Joel Lexchin, MD, is associated with the School of Health Policy and Management at York University in Toronto. He reported financial affiliations with the Gordon and Betty Moore Foundation, the Government of Canada, the Ontario Supporting Patient Oriented Research Support Unit, the St Michael’s Hospital Foundation, the Canadian Institutes of Health Research, and the American Diabetes Association. These comments are adapted from his editorial. (JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410 ).
One question that remains from the study by Skydel et al. is why the Food and Drug Administration did not mandate postapproval clinical studies for more than one-third of the novel agents approved from 2009 to 2012.
Among 600 postapproval trials affiliated with pharmaceutical companies, the vast majority were for novel therapeutics being studied in oncology- and hematology-related indications. Many of these premarket trials are one-arm, nonrandomized studies approved with evidence from surrogate outcomes. Recent studies have revealed that many novel agents do not show an overall survival benefit 5 years post approval.
From a clinical perspective, interpreting safety and efficacy data from these trials is challenging because of various limitations, including small sample sizes, no control groups, and lack of randomization. High-quality evidence helping clinicians determine which patients will benefit from these novel therapeutics is needed.
In addition, the purpose of these sponsored studies has come into question. While they can be used to generate further clinical data, many other reasons are possible. The expectation could be that once these studies are complete, clinicians may prescribe the agent being examined, thereby increasing off-label prescribing. Recent studies have revealed that off-label prescribing has the potential to increase the risk of drug-related adverse events.
“Postapproval studies need to advance clinical care by answering unresolved questions,” Dr. Lexchin wrote. “Clinicians and patients deserve better.”
Joel Lexchin, MD, is associated with the School of Health Policy and Management at York University in Toronto. He reported financial affiliations with the Gordon and Betty Moore Foundation, the Government of Canada, the Ontario Supporting Patient Oriented Research Support Unit, the St Michael’s Hospital Foundation, the Canadian Institutes of Health Research, and the American Diabetes Association. These comments are adapted from his editorial. (JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410 ).
The majority of postapproval clinical trials conducted by pharmaceutical companies explored novel or expanded uses as opposed to monitoring original indications, according to results from a cross-sectional study.
“The U.S. Food and Drug Administration can use postmarketing requirements to mandate pharmaceutical companies to conduct clinical trials after the approval of novel therapeutics,” wrote Joshua J. Skydel of Tufts University, Boston, and colleagues in JAMA Network Open.
“From 2009 through 2012, the FDA approved 110 novel therapeutics for 120 indications,” the researchers reported.
Of those approved, 37 novel agents were identified that lacked requirements for postmarket monitoring. Data was obtained from the Drugs@FDA database and consisted of industry-sponsored postapproval clinical studies conducted in the United States.
Postapproval study information included 600 trials registered on ClinicalTrials.gov that were primarily aimed at producing additional efficacy and safety data in approved or unapproved uses. The majority of these trials were for novel therapeutics being evaluated in oncology- and hematology-related indications.
After analysis, the researchers found that most of these trials examined agents for novel or expanded indications (60.5%) or widened populations of the initially indicated condition (20.3%).
In addition, several of these studies were nonrandomized (59.8%), had small sample sizes (median, 44 participants), and did not include comparators (63.5%).
“Among 600 trials, only 12.0% exclusively evaluated the originally approved indication,” the authors wrote.
The researchers acknowledged that a key limitation of the study was the inclusion of only postapproval clinical studies affiliated with pharmaceutical companies.
“The FDA may need to impose additional postmarketing requirements to generate further evidence for the original indications,” they concluded.
The study was funded by the Tufts University School of Medicine and the Laura and John Arnold Foundation. The authors reported financial affiliations with Johnson & Johnson, Medtronic, the Blue Cross Blue Shield Association, the National Institutes of Health, the Laura and John Arnold Foundation, and the Food and Drug Administration.
SOURCE: Skydel JJ et al. JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410.
The majority of postapproval clinical trials conducted by pharmaceutical companies explored novel or expanded uses as opposed to monitoring original indications, according to results from a cross-sectional study.
“The U.S. Food and Drug Administration can use postmarketing requirements to mandate pharmaceutical companies to conduct clinical trials after the approval of novel therapeutics,” wrote Joshua J. Skydel of Tufts University, Boston, and colleagues in JAMA Network Open.
“From 2009 through 2012, the FDA approved 110 novel therapeutics for 120 indications,” the researchers reported.
Of those approved, 37 novel agents were identified that lacked requirements for postmarket monitoring. Data was obtained from the Drugs@FDA database and consisted of industry-sponsored postapproval clinical studies conducted in the United States.
Postapproval study information included 600 trials registered on ClinicalTrials.gov that were primarily aimed at producing additional efficacy and safety data in approved or unapproved uses. The majority of these trials were for novel therapeutics being evaluated in oncology- and hematology-related indications.
After analysis, the researchers found that most of these trials examined agents for novel or expanded indications (60.5%) or widened populations of the initially indicated condition (20.3%).
In addition, several of these studies were nonrandomized (59.8%), had small sample sizes (median, 44 participants), and did not include comparators (63.5%).
“Among 600 trials, only 12.0% exclusively evaluated the originally approved indication,” the authors wrote.
The researchers acknowledged that a key limitation of the study was the inclusion of only postapproval clinical studies affiliated with pharmaceutical companies.
“The FDA may need to impose additional postmarketing requirements to generate further evidence for the original indications,” they concluded.
The study was funded by the Tufts University School of Medicine and the Laura and John Arnold Foundation. The authors reported financial affiliations with Johnson & Johnson, Medtronic, the Blue Cross Blue Shield Association, the National Institutes of Health, the Laura and John Arnold Foundation, and the Food and Drug Administration.
SOURCE: Skydel JJ et al. JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410.
FROM JAMA NETWORK OPEN
Key clinical point: The majority of postapproval clinical trials conducted by pharmaceutical companies explored novel or expanded uses as opposed to monitoring original indications.
Major finding: Among 600 postapproval studies, only 12.0% solely examined the original therapeutic indication.
Study details: A cross-sectional analysis of 37 novel agents without postmarketing requirements.
Disclosures: The study was funded by the Tufts University School of Medicine and the Laura and John Arnold Foundation. The authors reported financial affiliations with Johnson & Johnson, Medtronic, the Blue Cross Blue Shield Association, the National Institutes of Health, the Laura and John Arnold Foundation, and the Food and Drug Administration.
Source: Skydel JJ et al. JAMA Netw Open. 2019 May 9. doi: 10.1001/jamanetworkopen.2019.3410.